Annals of Oncology Advance Access published online on December 1, 2005
Annals of Oncology, doi:10.1093/annonc/mdj095
1 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC - Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
* To whom correspondence should be addressed. Background: Studies comparing survival in BRCA1-associated and sporadic breast cancer (BC) report inconsistent results and frequently concern small sample sizes. Further, the prognostic impact of the classical tumour and treatment factors is unclear in BRCA1-associated BC. Patients and methods: We selected 223 BC patients diagnosed between 1980 and 2001 within families with a deleterious germline BRCA1-mutation ascertained at the Rotterdam Family Cancer Clinic. To correct for ascertainment bias, the group of index patients undergoing DNA testing more than 2 years after BC diagnosis (n = 53) was separated from the other BRCA1-patients (n = 170). All BRCA1-associated patients were matched in a 1:2 ratio for age and year of diagnosis to sporadic BC patients. We compared the occurrence of ipsi- and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS). By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in BRCA1-associated and sporadic breast cancers. Results: For the total group of 669 cases, the median follow-up was 5.1 years, the median age at diagnosis 39 years. We confirmed the existence of the typical BRCA1-associated tumour type and the high CBC incidence. No significant differences between BRCA1-associated and sporadic tumours were found with respect to ipsilateral BC recurrence (HRmult 0.7; P = 0.24), DDFS (HRmult 1.2; P = 0.37) or BC-specific survival (HRmult 1.3; P = 0.23). A trend towards a worse survival was found for BRCA1-associated ductal BC (HRmult 1.5, P = 0.07). Prognostic factors for BRCA1-associated BC were age at diagnosis, tumour size and morphology, and nodal status. Further, survival was non-significantly improved by systemic treatment and a bilateral salpingo-oophorectomy. No effect on survival of a contralateral prophylactic mastectomy was seen. Conclusions: BRCA1-associated BC is characterised by specific tumour characteristics, a high incidence of CBC and a trend towards a worse survival for the ductal tumour type. Our observation that tumour size and nodal status are also prognostic factors for BRCA1-associated BC implies that the strategy to use these factors as a proxy for ultimate mortality, for instance in BC screening programmes or the consideration of (contralateral) preventive mastectomy, appears to be valid in this specific group of patients.
Received August 10, 2005
Revised October 28, 2005
Accepted November 4, 2005
original article
Survival and prognostic factors in BRCA1-associated breast cancer
C. T. M. Brekelmans 1 *,
C. Seynaeve 1,
M. Menke-Pluymers 2,
H. T. Brüggenwirth 3,
M. M. A. Tilanus-Linthorst 2,
C. C. M. Bartels 2,
M. Kriege 1,
A. N. van Geel 2,
C. M. G. Crepin 1,
J. C. Blom 1,
H. Meijers-Heijboer 3,
and
J. G. M. Klijn 1
2 Department of Surgical Oncology, Family Cancer Clinic, Erasmus MC - Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
3 Department of Clinical Genetics, Family Cancer Clinic, Erasmus MC - Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
C. T. M. Brekelmans, E-mail: c.brekelmans{at}erasmusmc.nl
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